1. Field of the Invention
This invention is directed to novel substituted phenylacetic acid ester compounds which are useful as short-acting sedative hypnotic agents for anesthesia and sedation. This invention is also directed to pharmaceutical compositions comprising such compounds; methods for using such compounds for inducing or maintaining anesthesia or sedation; and intermediates for preparing such compounds.
2. State of the Art
Propofol, 2,6-diisopropylphenol, (Diprivan® Injectable Emulsion, AstraZeneca) is an injectable anesthetic that has hypnotic properties. It can be used to induce and maintain general anesthesia and for sedation. Although propofol is a widely-used anesthetic, its usefulness is somewhat limited due to its long and unpredictable post infusion duration of action. This unpredictable duration of action leads to irregular and often long patient recovery times that are undesirable.
Propanidid [4-[(N,N-diethylcarbamoyl)methoxy]-3-methoxyphenyl]acetic acid propyl ester), is another injectable anesthetic that has been approved for use in several countries outside the United States. Although propanidid provides a much shorter and predictable recovery time than propofol, it is not as potent an anesthetic. Additionally, Epontol®, an injectable emulsion formulation of propanidid, provided by Bayer, was withdrawn from the market in Great Britain in 1983 because of concern over anaphylactoid reactions. Thus, in spite of the fact that propanidid provides shorter and more predictable recovery times than propofol, it has not been accepted widely as an injectable anesthetic.
Currently there is a need for novel injectable anesthetic agents. Preferred agents will have a shorter and more predictable duration of action than propofol. Preferred agents will also be more potent than propanidid.